Journal
JOURNAL OF LIPID RESEARCH
Volume 54, Issue 7, Pages 1980-1987Publisher
ELSEVIER
DOI: 10.1194/jlr.M034132
Keywords
apolipoproteins; cholesterol-lowering drugs; lipids; rare variants; fenofibric acid; high density lipoprotein
Categories
Funding
- Abbott Laboratories, Abbott Park, IL
- Department of Veterans Affairs Health Services Research and Development Career Development Award
- Merck
- Abbott
- Amarin
- AstraZeneca
- Bristol-Myers Squibb
- GlaxoSmithKline
- Genentech
- Kowa
- Novartis
- Roche
- Sanofi-Synthelabo
- Takeda
- American Diabetes Association
- American Heart Association
- National Institutes of Health
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Individuals with mixed dyslipidemia, including high triglycerides (TGs) and low high density lipoprotein cholesterol (HDL-C), have increased risk for coronary events. We examined the effect of rare genetic variants in the APOA5 gene region on plasma HDL-C, apolipoprotein A-I (apoA-I), and TG response to fenofibric acid monotherapy and in combination with statins. The APOA5 gene region was sequenced in 1,612 individuals with mixed dyslipidemia in a randomized trial of fenofibric acid alone and in combination with statins. Student's t-test and rare variant burden tests were used to examine plasma HDL-C, apoA-I, and TG response. Rare APOA5 promoter region variants were associated with decreased HDL-C and apoA-I levels in response to fenofibric acid therapy; rare missense variants were associated with increased TG response to combination therapy. Further study is needed to examine the effect of these rare variants on coronary outcomes in this population in response to fenofibric acid monotherapy or combined with statins
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